Abstract
The rise of SARS-CoV-2 variants has made the pursuit to define correlates of protection more troublesome, despite the availability of the World Health Organisation (WHO) International Standard for anti-SARS-CoV-2 Immunoglobulin sera, a key reagent used to standardise laboratory findings into an international unitage. Using pseudotyped virus, we examine the capacity of convalescent sera, from a well-defined cohort of healthcare workers (HCW) and Patients infected during the first wave from a national critical care centre in the UK to neutralise B.1.1.298, variants of interest (VOI) B.1.617.1 (Kappa), and four VOCs, B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta), including the B.1.617.2 K417N, informally known as Delta Plus. We utilised the WHO International Standard for anti-SARS-CoV-2 Immunoglobulin to report neutralisation antibody levels in International Units per mL. Our data demonstrate a significant reduction in the ability of first wave convalescent sera to neutralise the VOCs. Patients and HCWs with more severe COVID-19 were found to have higher antibody titres and to neutralise the VOCs more effectively than individuals with milder symptoms. Using an estimated threshold for 50% protection, 54 IU/mL, we found most asymptomatic and mild cases did not produce titres above this threshold.
Highlights
SARS-CoV-2 is the causative agent of the COVID-19 pandemic, resulting in more than 200 million cases and over 4 million deaths [1]
COVID-19 patients hospitalised during the first wave and as well as NHS healthcare workers working at RPH served as the exposed HCW cohort
The serological screening used to classify convalescent HCW as positive or negative was done according to the results provided by a CE-validated Luminex assay detecting N, RBDand S-specific IgG [30], a lateral flow diagnostic test (IgG/IgM) and an Electro-chemiluminescence assay (ECLIA) detecting N- and S-specific IgG
Summary
SARS-CoV-2 is the causative agent of the COVID-19 pandemic, resulting in more than 200 million cases and over 4 million deaths [1]. A number of single amino acid mutations in the Spike protein were detected, such as D614G and A222V. The D614G mutation was found to increase the density of Spike protein on virions and infectivity [4]. The rise of variants in circulation containing several mutations in the viral genome altered several properties of the virus [5]. Mutations found in the N-terminus and receptor-binding domain (RBD) of the Spike protein are associated with immune evasion [6–8]. Antibodies generated from prior infection or vaccination against the initial virus may provide reduced protection against new variants, giving rise to subsequent waves of infection in regional populations previously impacted by earlier COVID-19 outbreaks [11–13]
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